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Coccidioidomycosis

Using comparative genomics to identify Coccidioides virulence factors

Anita Sil, UC San Francisco/John Taylor, UC Berkeley

Abstract:
The environmental fungal pathogens Coccidioides and Histoplasma have been proposed as agents of warfare because of their easy availability, stability of spores, and infection by aerosolization. Therefore, more knowledge about the pathogenesis of these closely related organisms is critical to biodefense. Each of these organisms converts to a parasitic form in mammalian hosts after inhalation of infectious spores from the soil. We aim to understand their pathogenesis by identifying fungal genes that promote disease and manipulate the host. Use of a comparative genomics approach to analyze Coccidioides and Histoplasma is likely to be fruitful because of their close evolutionary relationship and the similarities of their lifestyles in the soil and the host. We will take advantage of information inherent in the genomes of these pathogens and related fungi to generate a set of genes most likely to influence disease. This comparative approach will reveal genes that have undergone strong positive selection in these fungal pathogens. Additionally, we will identify conserved genes in Coccidioides and Histoplasma that are implicated in the conversion to the parasitic form of each organism by virtue of their role in Histoplasma. These studies will allow us to prioritize a testable number of candidate virulence genes that will be assessed for their role in pathogenicity in the mouse models of Coccidioides and Histoplasma infections.